WO2014140236A1

WO2014140236A1 - Top dress feeding of zilpaterol in cattle

Info

Publication number: WO2014140236A1
Application number: PCT/EP2014/055050
Authority: WO
Inventors: John HUTCHESON; David Yates; Mary WRAY; John GRAETTINGER
Original assignee: Intervet International B.V.; Intervet Inc.
Priority date: 2013-03-15
Filing date: 2014-03-14
Publication date: 2014-09-18

Abstract

A method of improving the efficiency of beef production of a bovine animal comprising delivering to the animal an effective dose of zilpaterol of 60 to 90 mg/head/day as a top dress feed.

Description

TOP DRESS FEEDING OF ZILPATEROL IN CATTLE

The present invention relates to a method of improving the efficiency of beef production from a bovine animal comprising delivering to the animal an effective dose of zilpaterol and to a cattle feed to be used in such a method.

BACKGROUND OF THE INVENTION In intensive production systems, bovine animals such as cattle, are fed in environments with limited areas, such as in stalls, pens and feedlots in high stocking densities.

Ruminant animals, such as beef cattle, are classified as herbivores, meaning they can survive and produce while feeding chiefly on grass or other roughage feed ingredients consisting of large amounts of cellulose. However, cattle which are being intensively produced for slaughter will normally be placed in a confined feeding facility (feedlot) at 7-15 months of age, and fed growing diets consisting of 30-60% roughage and/or finishing diets consisting of only 5-15% roughage (conventional finishing ration on a dry basis), the roughage will normally be in the form of hay, silage, fodder, corn cobs, cottonseed hulls, etc. The remainder of the diet will consist of a high energy grain source such as corn, grain sorghum, barley, wheat, grain by-products, etc., and properly balanced for energy, protein, fibers, minerals and vitamins.

Such diets are formulated according to the specific requirements of the target animal mostly by commercial feed mill operations as meal type, pellets or crumbles.

In general commercially prepared feeds are in the form of: 1. complete feeds or rations that provide all the daily required nutrients, 2. concentrate feeds that provide a part of the ration (protein, energy) that are often combined with roughage such as hay or silage, or 3. feed supplements that only provide additional micronutrients, such as minerals and vitamins in the form of meals, pellets or crumbles.

It is an important goal of livestock producers to optimize efficiency of feed conversion of the feedlot diet into edible human food products of high quality, without posing any significant risk to the consumer. A number of approaches have become very common to improve conversion of animal feed into meat, three of the more practical approaches being

supplementing the animal feed with (i) hormones, (ii) adrenergic β-agonist compounds or (iii) antimicrobial- and ionophore medicated feed additives. Whereas, the antimicrobial additive approach aims at decreasing populations of pathologic bacteria in the hosts' gastro-intestinal (GI) tract, β-agonist compounds preferentially increase nutrient partitioning to muscle. The two commercially available β-agonist compounds for use in beef cattle production are ractopamine and zilpaterol. Frequently used antimicrobial feed additives in cattle include monensin and tylosin. Melengestrol acetate (MGA) is another orally active feed additive commonly used in feedlot animals that suppresses recurrent estrus and increases growth rate and improves feed efficiency in heifers.

Currently, in most intensive production systems, such a feed lots, cattle feed is mixed and typically distributed 2 to 3 time per day. In practice, all the animals in a single pen receive the same feed at any given meal or feeding. However, animals are grouped in pens based on similar characteristics such as size, sex and age. Each grouping or pen may require different feed requirements based on the aforementioned characteristics.

This is particularly true when there are feed additives that are mixed into the feed. For example, while all cattle may be fed certain feed additives such as monensin and tylosin, only heifers are fed melengestrol acetate (MGA). Further, zilpaterol is only administered to animals during the last 20- 40 days prior to slaughter. Therefore, the mixing of different feed compositions for different pens can be a complicated and often laborious process. For example, many feed lots are mixing feed compositions for the cattle requiring zilpaterol 2-3 times per day in every feeding. If the feedlot has pens of heifers, yet another feed

composition containing zilpaterol and MGA is required to be prepared several times per day for those particular pens of cattle. Moreover, distribution of each feed composition to the correct pen adds complexity to the task of feeding the cattle and can be a source of error which requires management attention.

Hence, there is a long felt need for a method of increasing efficiency of beef production in bovine animals that produces, at least, equivalent results to the current feed practices, but that, at the same time, can reduce the complexity of these feeding operations. Zilpaterol is a known adrenergic -2 agonist corresponding in structure to Formula (I):

The IUPAC name for zilpaterol is 4,5,6,7-tetrahydro-7-hydroxy-6-(isopropylamino) imidazo[4,5,l-jk]-[l]benzazepin-2(lH)-one. The Chemical Abstracts name for zilpaterol is 4,5,6,7-tetrahydro-7-hydroxy-6-[(l-methyl-ethyl) amino] -imidazo [4,5,l-jk][l]benzazepin- 2(lH)-one.

Zilpaterol hydrochloride is sold by Merck Animal Health, under the trademark Zilmax^®. It is approved in the United States for increased rate of weight gain, improved feed efficiency, and increased carcass leanness in cattle fed in confinement for slaughter during the last 20 to 40 days on feed. The approved inclusion rate of zilpaterol hydrochloride is 6.8 grams/ton (7.5 ppm) in feed on a 90% dry matter basis that is fed continuously as a sole ration in the last 20- 40 days of the animal's life prior to slaughter. See NADA No. 141-258. In U.S. Patent 4,585,770, Frechet et al. discuss compounds, such as zilpaterol, encompassed by a genus characterized as 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][l]- benzazepin-2-(lH)-one derivatives and acid addition salts thereof. Frechet et al. state that such compounds may be used as an active ingredient for inducing antihypertensive and hypotensive activity in a warm-blooded animal.

In U.S. Patent 4,900,735, Grandadam discusses a zootechnical composition comprising zilpaterol and acid addition salts thereof. Grandadam states that such a composition may be used in general to increase the weight of cattle, pigs, sheep, and poultry. In U.S. Patents 5,731,028 and 5,847,124, Chevremont et al. discuss crystallized anhydrous zilpaterol hydrochloride, and particularly crystallized anhydrous zilpaterol hydrochloride wherein less than 5% of the crystals have a size of less than 15 μιη, and at least 95% of the crystals have a size of less than 250 μηι. According to Chevremont et al, such crystals may be incorporated into animal feed to increase body weight and meat quality.

U.S. Patent Application Publication No. US 2010/0121050 and No. US 2012/0058189 disclose a process for making zilpaterol, salts - and crystalline forms thereof, as well as various administration methods and - regimes for a variety of livestock animals.

Ractopamine hydrochloride is another β-agonist that is currently added to feed in order to increase the growth performance of cattle and swine.

The effects of both ractopamine and zilpaterol on finishing performance, carcass

characteristics and meat quality of feedlot steers when fed according to a customary schedule of twice a day feeding of a complete diet is, for example, reported in Avendano -Reyes et al. (J. Animal Sciences 84, 3259-3265, 2006), and Elanco Optaflexx® Research Briefs 3-5, 2011-2012.

Top dress feeding of feed additives to cattle is an alternative to complete feeding programs that increases flexibility to the cattle producer and at the same time reduces labor- and feed- manufacturing costs. This allows farmers to target pens of cattle with unique needs that, in particular, exist in feedlots.

Alternative methods of delivering the zilpaterol and ractopamine feed additives have been developed (Gonzalez et al, Florida Beef Report 2009, 77-82; O'Neill et al, S. African Journal Anim. Science 40, 185-189, 2010; Freedom of Information Summary, Supplemental New Animal Drug Application NAD A 141-221).

SUMMARY OF THE INVENTION

In an embodiment, the invention is a method of improving the efficiency of beef production from a bovine animal comprising delivering to the animal an effective dose of zilpaterol of 60 to 90 mg/head/day as a top dress feed.

In another embodiment of the method one or more of the variables average daily gain (ADG) and feed efficiency (FE) of the animal are increased. In another embodiment of the method one or more of the variables hot carcass weight, dressing percentage, ribeye area and carcass leanness are increased.

In another embodiment of the method carcass leanness is increased. In another embodiment of the method the animal is fed multiple times per day and the top dress feed is delivered in one or more but not all of daily feedings.

In another embodiment of the method the top dress feed is delivered in one of the daily feedings.

In another embodiment of the method the top dress feed is added on top of the animal's complete feed.

In another embodiment of the method the complete feed is a medicated feed comprising one or more feed additives selected from the group of tylosin, monensin and MGA.

In another embodiment of the method the animal is fed in confinement for slaughter during the last 20 to 40 days on feed. In another embodiment of the method the confinement is in a feedlot. In another embodiment of the method the concentration of zilpaterol in the top dress feed is from about 6.8 to about 360 g/ton when feeding a minimum of 0.5 lb of the top dress feed per day to the animal. In another embodiment of the method the concentration of zilpaterol in the top dress feed is from about 6.8 to about 180 g/ton when feeding a minimum of 1.0 lb of the top dress feed per day to the animal.

In another embodiment of the method the concentration of zilpaterol in the top dress feed is 120 g/ton.

In another embodiment of the method the concentration of zilpaterol in the top dress feed is 180 g/ton. In another embodiment of the method the effective dose of zilpaterol is 90 mg/head/day. In another embodiment of the method the top dress feed is a Type B- or Type C medicated feed.

Another embodiment of the invention is a method of improving the efficiency of beef production from a bovine animal comprising mixing a Type A medicated article comprising zilpaterol into a Type B- or Type C medicated top dress feed to provide 60-90 mg/head/day zilpaterol and delivering the top dress feed to the animal.

In another embodiment the method the medicated top dress feed comprises from about 6.8 to about 180 g/ton zilpaterol.

In another embodiment of the method the medicated top dress feed is delivered in one of the daily feedings. In another embodiment of the method the animal is fed in confinement for slaughter during the last 20 to 40 days on feed. In another embodiment of the method the Type A medicated article comprises 48g/kilogram zilpaterol hydrochloride.

In another embodiment of the method one or more of the variables selected from the group consisting of average daily gain (ADG), feed efficiency (FE), hot carcass weight, dressing percentage, ribeye area and carcass leanness are increased.

Another embodiment of the invention is a cattle feed composition comprising zilpaterol in a concentration of 100 to 360 g/ton.

In another embodiment of the cattle feed composition the zilpaterol is in concentration of 100 to 180 g/ton.

In another embodiment of the cattle feed composition the zilpaterol concentration is 120 g/ton.

In another embodiment of the cattle feed composition the zilpaterol concentration is 180 g/ton.

In another embodiment of the cattle feed composition the feed composition is a Type C medicated top dress feed.

In another embodiment of the cattle feed composition the zilpaterol is zilpaterol hydrochloride. Definitions

"Dry matter intake" (DMI ) refers to the animal feed intake, usually per day, expressed in terms of its dry matter content.

"Average daily gain" (ADG) refers to body weight gain (lb) / number of days.

"Feed efficiency ratio" (FE) = DMI/ ADG. Improved feed efficiency means a decrease in the ratio DMI/ADG.

"Hot carcass weight" is the "hot" or unchilled weight in pounds (taken after slaughter and after the hide, head, intestinal tract and internal organs have been removed). "Dressing percentage" is determined by dividing the hot carcass weight by the live weight, then multiplying by 100.

"Improving the efficiency of beef production" means improvement in one or more of the live growth performance variables of ADG and FE or improvement in one or more of the carcass variables of hot carcass weight, dressing percentage, ribeye area and carcass leanness of a bovine animal that is fed zilpaterol containing feedings compared to a bovine animal that is fed feed without zilpaterol. "Bovine animal" refers to an animal of genus Bos taurus or Bos indicus, in particular cattle, buffalo, zebu or yak, more in particular cattle, that are raised to produce meat for human food, specifically, heifers, steers, cows and bulls.

"Top dress feed" is a feed comprising an active ingredient that is generally delivered to an animal in small amounts added on top of the animal's usual feed.

"Ton" is a unit of measure for mass equal 2000 lb.

"Metric ton (MT)" is a unit of measure for mass equal to 1000 Kg.

"ppm" is an abbreviation of parts per million, ppm is a value that represents the part of a whole number in units of 1/1000000. "ppm' is dimensionless quantity, a ratio of 2 quantities of the same unit. For example, a 5 ppm concentration of zilpaterol means 5 mg of zilpaterol per 1 kg of feed. In another example, a 5 ppm concentration of zilpaterol means 5 g of zilpaterol per 1 metric ton (1000 kg) of feed, a 5 ppm concentration of zilpaterol means 4.55 g of zilpaterol per 1 ton (2000 lb) of feed.

"Zilpaterol" means 4,5,6,7-tetrahydro-7-hydroxy-6-(isopropylamino) imidazo[4,5,l-jk]- [l]benzazepin-2(lH)-one or any salts or solvates thereof. For example it also includes zilpaterol hydrochloride.

"Multiple times per day" means more than one feeding per day to an animal. "Effective amount" is an amount of zilpaterol sufficient to improve the efficiency of beef production from a bovine animal.

" ad libitum feeding " means food available at all times with the quantity and frequency of consumption being the free choice of the animal.

Types of Medicated Products (US 21 CFR § 558.3):

"Type A medicated article": (previously called Premix) is intended solely for use in the manufacture of another Type A medicated article or a Type B or Type C medicated feed. It consists of a new animal drug (s) with or without a carrier (e.g., calcium carbonate, rice hull, corn, gluten) with or without inactive ingredients.

"Type B medicated feed": (previously called Concentrate) is intended solely for the manufacture of other medicated feeds (Type B or Type C). It contains a substantial quantity of nutrients including vitamins and/or minerals and/or other nutritional ingredients in an amount not less than 25 percent of the weight. It is manufactured by diluting a Type A medicated article or another Type medicated feed.

"Type C medicated feed": is intended as the complete feed for the animal or may be fed "top dressed" (added on top of usual ration) on or offered "free-choice" (e.g., supplement) in conjunction with other animal feed. It contains a substantial quantity of nutrients including vitamins, minerals, and/or other nutritional ingredients. It is manufactured by diluting a Type A medicated article or a Type B medicated feed. A Type C medicated feed may be further diluted to produce another Type C medicated feed.

Other definitions for selected terms used herein will be found within the description of the invention and apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood by individuals who are skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION

An advantageous method of delivering a β-agonist feed additive to bovine animals has now been developed by the present inventors. This method is easier and more efficient for the user to execute than the existing feeding programs and at the same time affords equivalent efficiency of beef production results. In the Examples below, it is shown that when zilpaterol is delivered to cattle as a top dress feed in an effective dose of 60 to 90 mg/head/day, efficiency of beef production results can be obtained that are equivalent to those obtained in the currently used feeding program in the field where the zilpaterol is delivered to the animals in each complete feeding. A particular surprising result shown is that the favorable efficiency results can be obtained when the animal is fed multiple times per day and the top dress feed is delivered in one or more but not all of daily feedings. In a very advantageous method the top dress feed is delivered in one of the daily feedings. The methods of the invention offer increased flexibility of the feeding management on a farm with cattle feed facilities to the cattle producer as well as a reduction of labor- and feed-manufacturing costs.

Accordingly, in an embodiment the invention provides a method of improving the efficiency of beef production from a bovine animal comprising delivering to the animal an effective dose of zilpaterol of 60 to 90 mg/head/day as a top dress feed.

Whereas the favorable efficiency of beef production results can be obtained by a compound with the structure shown in formula 1 , or any salts or solvates thereof, zilpaterol

hydrochloride is preferably used in the methods and compositions according to this invention. The feeding program of this invention wherein animals generally receive zilpaterol in a small amount of feed added on top of the animals' usual feed is referred herein as "top dress feeding".

In an embodiment the methods and compositions of the present invention are useful for improving the "efficiency of beef production" of a bovine animal.

In a further embodiment the methods and compositions of the present invention are useful for improving one or more of live growth performance variables or - carcass variables.

In particular, in a method of the invention the variable average daily gain (ADG) is increased and/or the variable feed efficiency ratio (FE) is decreased.

In an alternative method of the invention one or more of the variables hot carcass weight, dressing percentage, ribeye area and carcass leanness are increased. In a particular embodiment of the invention carcass leanness is increased.

In embodiments of the invention the animal is fed multiple times per day and the top dress feed is delivered in one or more but not all of daily feedings.

In a more particular embodiment the top dress feed is delivered in one of the daily feedings. The exact nutrient composition and formulation of the top dress feed and the animals' usual feeds used herein are not critical to the present invention and can be based on the

compositions and formulations that are currently used in the field. The ingredients are selected according to the nutrient requirements of a particular animal for which the feeding is intended. Such requirements depend, for example, upon age, stage of development of the animal and the sex of the animal. Commonly used cattle feed compositions and formulations are published by the National Academy of Sciences, Nutrient Requirements of Beef Cattle, Appendix Tables 1-19, 192-214, National Academy Press (2000) and Merck Veterinary Manual (10^th Edition, 2010, Feeding and Nutritional management of Beef cattle.).

In particular, the feed useful in the practice of the present invention include forages and grain feeds, such as grass and legume forages, crop residues, cereal grains, legume by-products and other agricultural by-products. As used herein, "forages" include the cut aerial portion of a plant material, both monocotyledonous and dicotyledonous, used as animal feed. Examples include, without limitation, orchard grass, timothy, tall fescue, ryegrass, alfalfa, sainfoin, clovers and vetches. With "grain feeds," are meant the seeds of plants that are fed to ruminant animals and may or may not include the outer hull, pod or husk of the seed. Examples include, without limitation, corn, wheat, barley sorghum, triticale, rye, canola, and soya beans.

In beef feedlots, young growing cattle are fed a high energy and high protein feeding to produce marketable beef at a low cost of gain. Mean nutrient contents of feeds commonly used in beef cattle diets, in particular of growing and finishing beef cattle is disclosed in the Merck Veterinary Manual (10^th Edition, 2010, Feeding and Nutritional management of Beef cattle, and Vasconcelos et al, J Anim Sci, 85, 2772-2781, 2007). Favorable crude protein (CP) content of feedings to be used herein are typically between 12-14% (w/w), more in particular between 12.5-13.5% (w/w). Optimal efficiency of beef production can be achieved when the bovine animals receive feedings with a total daily energy content of 1.37-1.70 MCal/kg net energy for gain (NEg), preferably 1.45-1.60 MCal/kg NEg. Accordingly, in a preferred method of the invention, the bovine animal receives feed with a total daily CP content of 12-14% (w/w), more in particular between 12.5-13.5% (w/w).

In another preferred method the bovine animal receives feed with a total daily NEg content of 1.37-1.70 MCal/kg, preferably 1.45-1.60 MCal/kg. In a preferred embodiment the top dress feed and usual feeds delivered to the animal are complete feeds, i.e. feeds that are balanced as to their nutrient composition. In a complete feed the roughage and the concentrate ingredients, including the protein, mineral, vitamin and other ingredients are all fed as one mixture. This means that the composition of a complete feed is such that it provides a balanced diet in each mouthful an animal consumes.

In a more specific embodiment the complete feed is a medicated feed, in particular a Type C medicated feed comprising one or more feed additives other than zilpaterol, such as tylosin, monensin and MGA. In accordance with the present invention the top dress feed comprises zilpaterol thoroughly mixed into the feed. Such mixed cattle feed can be produced by specialized commercial feed mills that blend the various raw materials and the feed additive according to the specifications outlined by an animal nutritionist by applying commonly used milling techniques. Such feed compositions are, preferably, produced by mixing nutritional feed ingredients with a premix comprising the zilpaterol. A premix to be used in the context of the present invention comprises zilpaterol and a suitable carrier or diluent. A preferred premix is a Type A medicated article comprising the zilpaterol. Carriers suitable for use to make up the feed composition may include the following: ground corn, alfalfa meal, soybean meal, cottonseed oil meal, linseed oil meal, sodium chloride, cornmeal, cane molasses, urea, bone meal, corncob meal, rice kernel and the like. The carrier promotes a uniform distribution of the active ingredient in the finished feed into which the carrier is blended. It thus performs an important function by ensuring proper distribution of the active ingredient throughout the feed.

Methods are known to one skilled in the art to determine and monitor whether the feed is thoroughly mixed to meet the required specifications (see Herrman et al, MF1172 and

MF2043, Kansas State University Agricultural Experimental Station and Cooperative

Extension Service, October 1994 and May 2002); US Food and Drug Administration (FDA) Current Good Manufacturing Practices regulation Title 21 C.F.R. 225.30,130). In an embodiment the top dress feed is a Type B medicated feed or a Type C medicated feed. The methods and compositions of the present invention can advantageously by applied in intensive production systems, such as feedlots, wherein cattle is kept and raised in confinement until slaughter and wherein efficiency of beef production of the animals is a key parameter that determines the economical success of the livestock producer (see also Merck Veterinary Manual, 10^th Edition, Management and Nutrition, 2010). Especially in intensive production systems, such as feedlots, cattle are often fed multiple times or meals per day. In feedlots, over 90% are fed 2-3 times per day (see Vasconcelos, et al. J. ANIM SCI 2007, 85 2772-2781).

The frequency of feedings, however, can be greater than 3 feedings per day.

Therefore, in a preferred embodiment, the method according to the invention comprises improving the efficiency of beef production of cattle, in particular heifers and/or steers, that are kept in confinement, such as in a feedlot. In a more specific embodiment the method according to the invention is used with cattle fed in confinement for slaughter during the last 20-40 days on feed.

The amount of top dress feed consumed in a meal (intake lb/meal) can vary between animals. In general, a dose of 60 to 90 mg/head/day is achieved when an (700-1300 lb) animal on complete feed eats 2-3% of body weight at a zilpaterol inclusion rate in feed of 6.8 g/ton. In the context of the present invention a 60-90 mg/head/day zilpaterol feeding rate is achieved in case the concentration of zilpaterol in the top dress feed is 6.8 to 360 g/ton when feeding the animal at a minimum of 0.5 lb of the top dress feed per day. In an alternative feeding program a 60-90 mg/head/day zilpaterol feeding rate is achieved in case the concentration of zilpaterol in the top dress feed is 6.8 to 180 g/ton when feeding the animal at a minimum of 1.0 lb of the top dress feed per day.

Therefore, in an embodiment, the zilpaterol concentration in the top dress feed (when expressed in grams of zilpaterol per ton of feed on a 90% dry mater basis) is from 6.8 g/ton to 360 g/ton when feeding a minimum of 0.5 lb of the top dress feed per day to the animal. In a further embodiment, the zilpaterol concentration in the top dress feed (when expressed in grams of zilpaterol per ton of feed on a 90% dry mater basis) is from 6.8 g/to 180 g/to when feeding a minimum of 0.5 lb of the top dress feed per day to the animal. Preferably, the zilpaterol concentration is 120 g/ton or 180 g/ton. The present invention also provides a Type A medicated article comprising zilpaterol, preferably comprising 48 g/kilo zilpaterol hydrochloride, intended for use in the manufacture of medicated animal top dress feed, such as a type Type C medicated top dress feed, such that the Type C medicated top dress feed provides an effective dose of zilpaterol of 60 to 90 mg/head/day. An example of a useful Type A medicated article is Zilmax^® (commercially available from Intervet Inc, US). Zilmax^® is an example of zilpaterol containing Type A medicated article and comprises 4.8% zilpaterol (w/w), 48 g/kg).

The Type A medicated article can be diluted prior to the addition to the Type C medicated feed by use of a micro-ingredient machine or via preparation of a Type B medicated feed.

Mixing directions for zilpaterol containing Type A medicated article:

Thoroughly mix zilpaterol containing Type A Medicated Article in a ton of appropriate feed ingredients or diluents according to the table below to obtain the proper concentration in the Type C Medicated Feed (minimum 6.8 g/ton, maximum 180 g/ton). The following table gives two examples of how Type C Medicated Feed concentrations can be prepared to provide 60 to 90 mg in a one pound Type C Medicated Feed: Table 1

Based on 90% dry matter basis

Feeding directions for zilpaterol containing Type C medicated feed:

Feed during one of the daily feedings to cattle fed in confinement for slaughter in a Type C Medicated Feed containing 6.8 to 180 g/ton zilpaterol hydrochloride to cattle in confinement for slaughter for the last 20 to 40 days on feed to provide 60 to 90 mg zilpaterol hydrochloride per head per day. The Type C Medicated Feed must be fed in a minimum of 1.0 lb of feed per head per day to provide 60 to 90 mg/head/day.

Accordingly, in an embodiment the invention provides a method of improving the efficiency of beef production from a bovine animal comprising mixing a Type A medicated article comprising zilpaterol into a Type B- or Type C medicated top dress feed to provide 60-90 mg/head/day zilpaterol and delivering the top dress feed to the animal.

In a more specific embodiment, the medicated top dress feed comprises 6.8 to 180 g/ton.

In a further embodiment the Type A medicated article comprises 48g/kilogram zilpaterol hydrochloride. In another embodiment the medicated top dress feed is delivered to the bovine animal fed in confinement for slaughter during the last 20-40 days on feed.

In a further embodiment delivering the medicated top dress feed results in an increase of one or more of the variables selected from the group consisting of average daily gain (ADG), feed efficiency (FE), hot carcass weight, dressing percentage, ribeeye area and carcass leanness. In again a further embodiment, the present invention also provides cattle feed that can advantageously be used in a method as described above. Such feed compositions may have the same or similar nutrient composition as those commonly used in the field by cattle producers, for example, as described in more detail above, but are distinguished therefrom by a higher concentration of zilpaterol (higher than 6.8 g. zilpaterol per ton feed).

Such a cattle feed composition is characterized in that it is intended for use as a top dress feed and comprises zilpaterol in a concentration of 100 to 360 g/ton, preferably 100 to 180 g/ton, in particular 120 g/ton or 180 g/ton.

In a specific embodiment the cattle feed is a Type C top dress feed and comprises zilpaterol hydrochloride.

Examples

Example 1 :

Clinical effectiveness study of zilpaterol containing top dress feed

The studies were conducted to examine the clinical effectiveness and field safety of 90 mg/head/day of Zilmax^® (Intervet Inc., USA) on body weight gain, feed efficiency, commercial carcass parameters and carcass leanness when fed to cattle in 0.5 lb of a pelleted Type C top dress supplement or via component feeding of 0.5 lb of a pelleted Zilmax^® supplement.

The effectiveness study design was a randomized complete block design. Cattle were randomized to one of four treatments by weight block and fed a Type C non-medicated complete feed twice daily during a 10-day acclimation period, a 40-day treatment period, and a 10-day withdrawal period in this study. During the 40-day treatment period, one of four pelleted supplement treatments was fed to each pen. The four treatments were:

Treatment Group 1 ("top dress"): a pelleted control (non-medicated) Type C top dress supplement containing no zilpaterol hydrochloride was fed once daily on top of the 1st feeding of non-medicated Type C feed to provide 0.5 lb of pelleted Type C top dress supplement per animal per day. Treatment Group 2 ("top dress"): a pelleted Zilmax^® containing Type C top dress supplement was fed once daily on top of the 1st feeding of non-medicated Type C feed to provide 90 mg zilpaterol hydrochloride in 0.5 lb of pelleted Type C top dress supplement per animal per day. Treatment Group 3 ("component fed"): a pelleted control (non-medicated) supplement was mixed into the 1st feeding of non-medicated Type C feed and fed to provide 0.5 lb of pelleted supplement per animal per day.

Treatment Group 4 ("component fed"): a pelleted Zilmax^® containing supplement was mixed into the 1st feeding of non-medicated Type C feed and fed to provide 90 mg zilpaterol hydrochloride in 0.5 lb of pelleted supplement per animal per day.

The "top dress" treatments were fed on top of the 1st issuance of non-medicated Type C feed after delivery to the feed bunks. The "component fed" treatments were mixed in the 1st issuance only of non-medicated Type C feed prior to feeding. All cattle were fed only the non-medicated Type C feed in a second feeding each day with no supplements added.

No ionophore or antibiotic was fed during the treatment or withdrawal phase. The cattle were fed a diet that had a NEg of 62.3 Mcal/cwt (1.37 Mcal/kg) on a dry matter basis.

Finishing steers were randomized by body weight to one of the four pelleted supplement treatment groups in pens of 10 head of finishing steers. Each of the four supplement treatments was fed to 12 pens. There were 480 head of steers included in the study. There was no negative effect of Zilmax^® administration via a pelleted top dress supplement or a pelleted component supplement on the health of the study animals.

Cattle were handled throughout the trials and at the termination of each trial, under conditions, which represent as closely as possible, commercial feedlot practices. Cattle were moved from the feedlot pens to the scale, individually weighed, and moved to the cattle loading area. Cattle were exposed to typical weather conditions during the spring, and summer months. Cattle were not held off feed prior to slaughter. Administration of Zilmax^® to finishing steers by component feeding or in a top dress supplement significantly improved average daily gain and feed efficiency over the combined 40-day treatment and 10-daywithdrawal periods compared to steers fed non-medicated component or top dress supplements. Dry matter intake over the performance period was significantly lower in cattle fed Zilmax^® by component feeding compared to cattle fed a non- medicated component supplement. There was no significant difference in dry matter intake between the non-medicated or Zilmax® top dress treatment groups (Table 2).

Hot carcass weight, dressing percentage and ribeye area were significantly greater in

Zilmax® fed cattle compared to cattle in the non-medicated groups regardless of feeding method. Steers in both the Zilmax® component and top dress treatment groups had significantly lower marbling scores, quality grades and calculated yield grades compared to the non-medicated steers. Fat thickness was not significantly different between the Zilmax® and non-medicated treatment groups, for both the top dress and component feeding groups (Table 3).

Carcass leanness was evaluated using carcass percent protein as the composition variable.

Carcass percent protein is the measure of the protein content in the carcass soft tissue which is ultimately merchandised as edible beef. Carcasses with increased levels of protein have a higher percentage of lean meat or red meat yield, and thus, more merchandisable red meat.

The effects of zilpaterol hydrochloride on carcass percent protein analysis were evaluated on a "wet weight" basis (i.e. calculations were not corrected for dry matter content).

Additionally, the effects of zilpaterol hydrochloride on carcass protein percentage were evaluated on an "equal weight" basis by collecting treated and control carcasses of similar hot carcass weights and quality grades. Sides of the "equal weight" carcasses were dissected and weights obtained for soft tissues, and bone (plus heavy connective tissue or any other inedible tissue such as glands, aorta, etc.). Bone and other inedible tissues were discarded after being weighed. The soft tissue from each carcass was ground, blended, frozen in liquid nitrogen, and powdered. Samples were analyzed for moisture, crude protein, ether extractable lipids, and ash. The average composition of the dissected carcass sides (two per pen for 46 pens, one per pen for two pens) represented the pen's carcass composition for statistical analysis. Change in carcass leanness was measured in differences in percent carcass protein which is defined as the tissue percent protein times the tissue weight, divided by the carcass weight, times 100.

Carcass leanness was significantly greater in Zilmax^® fed cattle compared to cattle in the non-medicated groups regardless of feeding method (Table 4). Based on the daily observations and field safety information collected, Zilmax^®

administration via a top dress or component supplement does not affect the health status of the study animals.

When fed at 90 mg zilpaterol hydrochloride/head/day in 0.5 lb of a pelleted Type C top dress supplement or via component feeding of 0.5 lb of pelleted Zilmax^® supplement, Zilmax^® increased rate of body weight gain, improved feed efficiency, and increased carcass leanness.

A summary of Zilmax effects on performance parameters is presented in Table 2. Table 2: Summary of the Statistical Analysis for the Effects of Zilmax^® on Performance

Variables (40-day Treatment and 10-day Withdrawal Periods)

o ga n

A summary of Zilmax effects on carcass variables is presented in Table 3.

Table 3 : Summary of the Statistical Analysis for the Effects of Zilmax^® on Label Panel

Carcass Variables (40-day Treatment and 10-day Withdrawal Periods).

w Marbling scores: 20-29 = Traces marbling; 30-39 = Slight marbling; 40-49 = Small marbling.

A summary of Zilmax^® effects on carcass protein percent, the indicator of carcass leanness, is presented in Table 4.

Table 4: Summary of the Statistical Analysis for the Effects of Zilmax^® on Carcass Protein Percent (40-day Treatment and 10-day Withdrawal Periods).

Component Feed Top Dress Feed

Factor Control Zilmax P-Value Control Zilmax P-Value

Carcass Protein, % 13.7 14.7 < 0.001 13.7 14.7 < 0.001

Claims

What is claimed is:

1. A method of improving the efficiency of beef production from a bovine animal comprising delivering to the animal an effective dose of zilpaterol of 60 to 90 mg/head/day as a top dress feed.

2. The method of claim 1, wherein the variable average daily gain (ADG) is increased or the variable feed efficiency ratio (FE) of the animal is decreased.

3. The method of claim 1, wherein one or more of the variables hot carcass weight, dressing percentage, ribeye area and carcass leanness are increased.

4. The method of claim 3, wherein carcass leanness is increased.

5. The method of claim 1, wherein the animal is fed multiple times per day and the top dress feed is delivered in one or more but not all of daily feedings.

6. The method of claim 5, wherein the top dress feed is delivered in one of the daily feedings.

7. The method of claim 1, wherein the top dress feed is added on top of the animal's complete feed.

8. The method of claim 7, wherein the complete feed is a medicated feed comprising one or more feed additives selected from the group of tylosin, monensin and MGA.

9. The method of claim 1, wherein the animal is fed in confinement for slaughter during the last 20 to 40 days on feed.

10. The method of claim 9, wherein the confinement is in a feedlot.

11. The method of claims 1 , wherein the concentration of zilpaterol in the top dress feed is from about 6.8 to about 360 g/ton when feeding a minimum of 0.5 lb of the top dress feed per day to the animal.

12. The method of claim 1, wherein the concentration of zilpaterol in the top dress feed is from about 6.8 to about 180 g/ton when feeding a minimum of 1.0 lb of the top dress feed per day to the animal.

13. The method of claim 12, wherein the concentration of zilpaterol in the top dress feed is 120 g/ton.

14. The method of claim 12, wherein the concentration of zilpaterol in the top dress feed is 180 g/ton.

15. The method of claim 1, wherein the effective dose of zilpaterol is 90 mg/head/day.

16. The method of any one of claims 1-15, wherein the top dress feed is a Type B- or Type C medicated feed.

17. A method of improving the efficiency of beef production from a bovine animal comprising mixing a Type A medicated article comprising zilpaterol into a Type B- or Type C medicated top dress feed to provide 60-90 mg/head/day zilpaterol and delivering the top dress feed to the animal.

18. The method of claim 17, wherein the medicated top dress feed comprises from about 6.8 to about 180 g/ton zilpaterol.

19. The method of claim 17, wherein the medicated top dress feed is delivered in one of the daily feedings.

20. The method of claim 17, wherein the animal is fed in confinement for slaughter during the last 20 to 40 days on feed.

21. The method of claim 17, wherein the Type A medicated article comprises 48g/kilogram zilpaterol hydrochloride.

22. The method of claim 17, wherein one or more of the variables selected from the group consisting of average daily gain (ADG), feed efficiency (FE), hot carcass weight, dressing percentage, ribeye area and carcass leanness are increased.

23. A cattle feed composition comprising zilpaterol in a concentration of 100 to 360 g/ton.

24. The cattle feed composition of claim 23, wherein the zilpaterol is in concentration of 100 to 180 g/ton.

25. The cattle feed composition of claim 23, wherein the zilpaterol concentration is 120 g/ton.

26. The cattle feed composition of claim 23, wherein the zilpaterol concentration is 180 g/ton.

27. The cattle feed composition of any one of claims 23-26, wherein the feed composition is a Type C medicated top dress feed.

28. The cattle feed composition of any one of claims 23 to 27 wherein the zilpaterol is zilpaterol hydrochloride.